A Case of Sustained Tumor Regression With MP0274, a Novel DARPin Therapeutic Targeting Human Epidermal Growth Factor Receptor 2 Signaling, in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer After Prior Trastuzumab and Pertuzumab

• DOI: 10.1200/po.22.00006
• Publication Date: 2022-11-03T19:59:36Z
• Authors: Stefanie Fischer; Thorsten O. Götze; Aurelius Omlin; Richard D. Baird; Keith M. Dawson; Christof Zitt; Zita Arany; Gaby Tresch; Ulrike Fiedler; Simone Jeger; Samson Fung; Philippe Legenne; Nicolas Leupin; Andreas Schneeweiss; Carlo Fremd
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Receptor, ErbB-2; Humans; Antineoplastic Agents; Breast Neoplasms; Designed Ankyrin Repeat Proteins; Female; Case Reports; Trastuzumab; 3. Good health

The human epidermal growth factor receptor 2 (HER2, ERBB2) is amplified or overexpressed in approximately 20% of breast cancers. HER2 amplification results in increased homodimerization and HER3 heterodimerization, with HER2/HER3 heterodimers promoting cell proliferation via the mitogen-activated protein kinase/AKT pathway and also evasion of apoptosis via the phosphatidylinositol 3-kinase (PI3K) signaling cascade. Oncogenic mutations in PI3KCA render tumor cells resistant to drugs that block HER2 dimerization, thereby promoting cell survival. Although several approved HER2-directed agents have shown significant survival improvements for HER2-positive patients, in the metastatic setting, nearly all of these patients will ultimately progress and die of their disease.